Chemical Modification of a Pepsin Inhibitor from the Activation Peptides of Pepsinogen

  • P. M. Harish Kumar
  • Peter H. Ward
  • Beatrice Kassell
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 92)


A pepsin inhibiting substance formed during the activation of porcine pepsinogen has been known for many years (1). Based on the finding that in solutions more acid than pH 4, the loss of pepsinogen was not immediately accompanied by an equivalent increase in pepsin. Herriott postulated the scheme shown in Figure 1 for the autocatalytic activation of pepsinogen. The pepsin inhibitor was separated and partially characterized by Herriott (2) and by Van Vunakis and Herriott (3,4). At that time, the techniques of peptide purification and amino acid analysis had not been perfected, and their analysis does not agree with any part of the amino-terminal sequence later elucidated by Ong and Perlmann (5). In 1973, however, Anderson and Harthill (6) prepared an inhibitor almost corresponding in composition to the amino-terminal 16 amino acids of porcine pepsinogen. A homologous 17-amino acid peptide from bovine pepsinogen was reported jointly by Foltmann’s group and by Kay and Kassell (7), while Kassell et al. (8) found a peptide from canine pepsinogen of similar composition to the first 14 amino acids of bovine pepsinogen. The high degree of homology of the amino-terminal portions of the pepsinogens of the three species, shown in Figure 2, makes it likely that the activation peptides are not simply “throw aways”, but have a physiological role. We have therefore returned to the porcine activation peptides for further investigation, since porcine pepsinogen is readily available.


Amino Acid Analysis Activation Peptide Edman Degradation Methane Sulfonic Acid Barium Hydroxide 
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  1. 1.
    Herriott, R. M. (1938) J. Gen. Physiol. 22, 65–78PubMedCrossRefGoogle Scholar
  2. 2.
    Herriott, R. M. (1941) J. Gen. Physiol. 24, 325–338PubMedCrossRefGoogle Scholar
  3. 3.
    Van Vunakis, H., and Herriott, R. M. (1956) Biochim. Biophys. Acta 22, 537–543CrossRefGoogle Scholar
  4. 4.
    Van Vunakis, H., and Herriott, R. M. (1957) Biochim. Biophys. Acta 23, 600–608CrossRefGoogle Scholar
  5. 5.
    Ong, E. B., and Perlmann, G. E. (1968) J. Biol. Chem. 243, 6104–6109PubMedGoogle Scholar
  6. 6.
    Anderson, W., and Harthill, J. E. (1973) Nature 243, 417–419PubMedCrossRefGoogle Scholar
  7. 7.
    Harboe, M., Andersen, P. M., Foltmann, B., Kay, J., and Kassell, B. (1974) J. Biol. Chem. 249, 4487–4494PubMedGoogle Scholar
  8. 8.
    Kassell, B., Wright, C. L., and Ward, P. H. (1976) Protides of the Biological Fluids–23rd Colloquium (Peeters, H. ed) pp. 541–544, Pergamon Press, Oxford and New YorkGoogle Scholar
  9. 9.
    Edman, P., and Begg, G. (1967) Eur. J. Biochem. 1, 80–91PubMedCrossRefGoogle Scholar
  10. 10.
    Nevaldine, B., and Kassell, B. (1971) Biochim. Biophys. Acta 250, 207Google Scholar
  11. 11.
    Kay, J. (1972) Fed. Eur. Biochem. Soc. Proc. Meet. Abstr. 458Google Scholar
  12. 12.
    Chervenka, C. H., and Wilcox, P. E. (1956) J. Biol. Chem. 222, 635–647Google Scholar
  13. 13.
    Kassell, B., and Chow, R. B. (1966) Biochemistry 5, 3449–3453PubMedCrossRefGoogle Scholar
  14. 14.
    Simpson, R. J., Neuberger, M. R., and Liu, T. Y. (1976) J. Biol. Chem. 251, 1936–1940Google Scholar
  15. 15.
    Eick, H. E., Ward, P. H., and Kassell, B. (1974) Anal. Biochem. 59, 482–488PubMedCrossRefGoogle Scholar
  16. 16.
    McPhie, P. (1976) Anal. Biochem. 73, 258–261PubMedCrossRefGoogle Scholar
  17. 17.
    Dunn, B. M., Moesching, W. G., Trach, M. L., Nolan, R. J., and Gilberts, W. A. (1976) Fed. Proc. 35, 1463Google Scholar
  18. 18.
    Peterson, J. D., Nehrlich, S., Oyer, P. E., and Steiner, D. F. (1976) J. Biol. Chem. 247, 4866–4871Google Scholar
  19. 19.
    Meagher, R. B. (1976) Anal. Biochem. 67, 404–412CrossRefGoogle Scholar
  20. 20.
    Konisberg, W., and Hill, R. J. (1962) J. Biol. Chem. 237, 2547–2561Google Scholar
  21. 21.
    Pedersen, V. B., and Foltmann, B. (1976) FEBS Lett. 35, 255–256CrossRefGoogle Scholar
  22. 22.
    Stepanov, V. M., Baratova, L. A., Pugacheva, I. B., Belyanova, L. P., Revina, L. P., and Timokhina, E. A. (1976) Biochem. Biophys. Res. Commun. 54, 1164–1170Google Scholar
  23. 23.
    Fraenkel-Conrat, H., Harriss, J. I., and Levy, A. L. (1955) in Methods of Biochemical Analysis, Vol. II (Glick, D. ed) pp. 359–425, Interscience, New YorkGoogle Scholar
  24. 24.
    Abita, J. P., Moulin, A., Lazdunski, M., Hage, G., Palasciano, G., Brasca, A., and Tiscornia, O. (1973) FEBS Lett. 34, 251–255PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1977

Authors and Affiliations

  • P. M. Harish Kumar
    • 1
  • Peter H. Ward
    • 1
  • Beatrice Kassell
    • 1
  1. 1.Department of BiochemistryMedical College of WisconsinMilwaukeeUSA

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